We have previously reported the presence of aryl hydrocarbon hydroxylase and epoxide hydrase in nuclei. We now plan to explore these findings more fully using 3-methylcholanthrene as an example of a polycyclic hydrocarbon which requires activation. The objectives of this research proposal are to: 1. ascertain if cytochrome P448 is found in nucleoli; 2. determine the metabolite spectrum after incubation of nuclei and cytosolic "receptor" proteins and determine the role of this interaction in the delivery of 3MC to the nucleus for metabolism; 4. ascertain the spectrum of adducts of 3MC (metabolites) to the DNA bases as formed in microsomal and nuclear systems and 5. establish the role of the various prostaglandins in the promotion phase of the 2-stage mechanism of skin tumorigenesis particularly in relation to 3MC-induced skin cancer.